Xavier Salvatella

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NMR spectroscopy plays a major role in the determination of the structures and dynamics of proteins and other biological macromolecules. Chemical shifts are the most readily and accurately measurable NMR parameters, and they reflect with great specificity the conformations of native and nonnative states of proteins. We show, using 11 examples of proteins(More)
Many biochemical processes proceed through the formation of functionally significant intermediates. Although the identification and characterization of such species can provide vital clues about the mechanisms of the reactions involved, it is challenging to obtain information of this type in cases where the intermediates are transient or present only at low(More)
Oligomerization in the heat shock protein (Hsp) 70 family has been extensively documented both in vitro and in vivo, although the mechanism, the identity of the specific protein regions involved and the physiological relevance of this process are still unclear. We have studied the oligomeric properties of a series of human Hsp70 variants by means of(More)
We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of(More)
Long-range correlated motions in proteins are candidate mechanisms for processes that require information transfer across protein structures, such as allostery and signal transduction. However, the observation of backbone correlations between distant residues has remained elusive, and only local correlations have been revealed using residual dipolar(More)
It has been shown recently that an 11-residue peptide fragment of transthyretin, TTR(105-115), can form amyloid fibrils in vitro by adopting an extended beta-strand conformation. We used molecular dynamics simulations on systems of TTR(105-115) peptides, for a total length of about 5 micros, to explore the process of self-assembly and the structures of the(More)
Residual dipolar couplings (RDCs) are unique probes of the structural and dynamical properties of biomolecules on the sub-millisecond time scale that can be used as restraints in ensemble molecular dynamics simulations to study the relationship between macromolecular motion and biological function. To date, however, this powerful strategy is applicable only(More)
Identifying the cause of the cytotoxicity of species populated during amyloid formation is crucial to understand the molecular basis of protein deposition diseases. We have examined different types of aggregates formed by lysozyme, a protein found as fibrillar deposits in patients with familial systemic amyloidosis, by infrared spectroscopy, transmission(More)
In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic(More)
The misfolding of proteins into amyloid fibrils constitutes the hallmark of many diseases. [1] Although relatively few phys-icochemical properties of protein sequences—charge, hydro-phobicity, patterns of polar and nonpolar residues, and tendency to form secondary structures—are sufficient to rationalize in general terms their relative propensities to form(More)